AB0192 ANTIBODIES AGAINST MODIFIED PROTEIN/PEPTIDE SPECIFICITIES IN RECENT-ONSET PALINDROMIC RHEUMATISM MAY DETERMINE THE EVOLUTION TO RHEUMATOID ARTHRITIS
Authors: C. García-Moreno, R. Morlà, B. Frade-Sosa, L. Tobalina, M. J. Gomara, R. Sanmartí, I. Haro
Journal: Annals of the Rheumatic Diseases (2022)

Background Palindromic rheumatism (PR) may evolve to rheumatoid arthritis (RA), particularly in patients with autoantibodies such as rheumatoid factor (RF) or antibodies against modified proteins (AMPA), anti-citrullinated peptide antibodies (ACPA) or anti-carbamylated antibodies (anti-CarP) (1,2). We hypothesized that the specificities and isotype usage of ACPA and anti-CarP may differ between recent-onset PR and established RA, and this could help ascertain the evolution to RA in PR patients. Objectives To determine differences in the recognition of epitopes between patients with recent-onset PR and established RA by analysis of AMPA specificities and isotypes. Methods Subanalysis using preliminary data of the PALABA study. Two populations included: patients with recent-onset PR include in the PALABA multicenter randomized clinical trial (abatacept vs hydroxychloroquine) at study entry ( NCT03669367 ) and patients with established RA (ACR/EULAR 2010) as controls previously selected from an observational study(3). Only RF and/or ACPA (CCP2) positive patients were selected. PR patients were DMARD naïve and RA patients receiving rituximab or abatacept were excluded. AMPA specificities and isotypes in sera were determined by in-house ELISA tests using as antigens two carbamylated proteins and a panel of chimeric peptides derived from fibrin and filaggrin proteins bearing one to three post-translational modifications (citrullination, carbamylation and acetylation) (4). The cut-off for ELISA tests was established by ROC curves, with a specificity of 95% compared with a healthy population. The frequency and titers of the AMPA isotypes (IgA,IgG,IgM) was analyzed. Results 45 PR patients (77.6% female), with a mean age of 49.3 (±11) years and a mean disease duration of 9.6 (±6.1) months and 125 RA patients (75.6% females) with a mean age of 59.6 (±13) years and a mean disease duration of 77.2 (±59.7) months. RF and ACPA (CCP2) were positive in 80% and 91.1% of PR patients and 77.6% and 88% of RA patients (p&gt;0.05). Although both populations presented a similar frequency of RF and ACPA(CCP2), PR patients had fewer AMPA specificities than RA patients. The differences were statistically significant for two IgA ACPA antigens (doubly citrullinated/homocitrullinated peptides) and most anti-CarP specificities and isotypes (Table). Table 1. Anti-CarP autoantibody status in RA vs PR patients. RA (n 125) PR (n 45) p value Fetal calf serum carbamylated (FCS-CarP) anti-FCS-CarP-IgG positive,n (%) 78 (62.4) 14 (31.1) &lt;0.005 median titer, AU/mL (IQR) 238 (571) 75 (249) &lt;0.005 anti-FCS-CarP-IgA positive,n (%) 41 (32.8) 2 (4.4) &lt;0.005 median titer, AU/mL (IQR) 161 (308) 14 (97) &lt;0.005 anti-FCS-CarP-IgM positive,n (%) 30 (24.0) 5 (11.1) NS median titer, AU/mL (IQR) 90 (165) 32 (101) &lt;0.005 Fibrinogen carbamylated (Fib-CarP) anti-Fib-CarP-IgG positive,n (%) 87 (69.6) 9 (20) &lt;0.005 median titer, AU/mL (IQR) 249 (304) 70 (104) &lt;0.005 anti-Fib-CarP-IgA positive,n (%) 25 (20.0) 10 (22.2) NS median titer, AU/mL (IQR) 0 (76) 36 (72) &lt;0.005 anti-Fib-CarP-IgM positive,n (%) 33 (26.4) 8 (17.8) NS median titer, AU/mL (IQR) 82 (117) 57 (84) NS Chimeric fibrin/filaggrin homocitrullinated peptide (CFFHP) anti-CFFHP-IgG positive,n (%) 54 (43.2) 10 (22.2) &lt;0.05 median titer, AU/mL (IQR) 9 (227) 0 (12) &lt;0.005 anti-CFFHP-IgA positive,n (%) 20 (16.0) 1 (2.2) &lt;0.05 median titer, AU/mL (IQR) 0 (5) 0 (0) NS anti-CFFHP-IgM positive,n (%) 14 (11.2) 2 (4.4) NS median titer, AU/mL (IQR) 0 (7) 0 (0) &lt;0.05 Conclusion The immune response against post-translational modified peptides/proteins has a lower frequency and less isotype usage in PR for some AMPA specificities in comparison with RA. The absence of IgA ACPA isotypes and, especially, anti-CarP in the early stages of PR may be associated with a lower rate of progression to RA. References [1]Cabrera-Villalba S et al. Arthritis Res Ther 2017 [2]Castellanos-Moreira R et al. Ther Adv Musculoskelet Dis 2020. [3]Castellanos-Moreira R et al. Ann Rheum Dis 2020 [4]García-Moreno et al. Int.J.Mol.Sci 2021 Acknowledgements PALABA study investigators: Beatriz Frade-Sosa, Rosa Maria Morlà, Lola Tobalina, Maria López-Lasanta, Helena Borrell, Georgina Salvador, Andrea M Cuervo, Noemí Busquets, Eduard Graell, Carolina Pérez- García, Luciano Pocino, Delia Reina, Oscar Camacho, Hector Corominas Ana M Millan. Miquel Sala, Sonia Castell, Eduardo Kanterewicz, Josep R. Rodriguez Cros, Alejandro Escudero, Usansolo Irati, José Francisco Garcia, Francisco Javier Toro, Natividad Oreiro, Alejandro Olivé, Maria J Gómara, Cristina García-Moreno, Isabel Haro and Raimon Sanmarti. Disclosure of Interests Cristina García-Moreno: None declared, Rosa Morlà: None declared, Beatriz Frade-Sosa: None declared, Lola Tobalina: None declared, Maria Jose Gomara: None declared, Raimón Sanmartí Speakers bureau: Received speaker honoraria from Abbvie, BMS, Gebro-Pharma, Lilly, MSD, Pfizer, Sanofi and Roche, Grant/research support from: investigation grants from Abbvie, BMS, Gebro-Pharma, Lilly, MSD, Pfizer, Sanofi and Roche, Isabel Haro: None declared